Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study
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The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls.
We performed PET using the 5-HTT selective radiotracer [11C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m2) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m2) in a cross-sectional study design. The 5-HTT binding potential (BPND) was used as the outcome parameter.
On a group level, there was no significant difference in 5-HTT BPND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BPND.
The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity.
KeywordsSerotonin Serotonin transporter Positron emission tomography (PET) Obesity Body mass index (BMI) Depression
We are very grateful to Damian McLeod, School of Biomedical Sciences and Pharmacy, University of Newcastle, Australia, for careful line editing and English proofreading of the first draft of the manuscript.
Compliance with ethical standards
This study was supported by the German Federal Ministry of Education and Research (FKZ: 01EO1001).
Conflict of interest
The authors report no conflicts of interest relating to the content of this manuscript.
All procedures performed in studies involving human participants were in accordance with the ICH Guideline for Good Clinical Practice (GCP) and with the 1964 Helsinki declaration and its later amendments. The study was approved by the ethics committee of the Medical Faculty of the University of Leipzig (registered under the number 206-10-08032010) and the German Bundesamt für Strahlenschutz/Federal Office for Radiation Protection (number Z5-22461-2-2011-002), and registered at the European clinical trial database EudraCT 2012-000568-32) and the German Clinical Trials Register (DRKS).
Informed consent was obtained from all individual participants included in the study.
- 3.Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245–56.CrossRefPubMedGoogle Scholar
- 9.Hesse S, Villringer A, Schönknecht P, Becker GA, Patt M, Bresch A, et al. Serotonin transporter (SERT) availability, body mass index (BMI) and depression. J Nucl Med. 2009;50 Suppl 2:1294.Google Scholar
- 13.Wilson AA, Ginovart N, Schmidt M, Meyer JH, Threlkeld PG, Houle S. Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of 11C-labeled 2-(phenylthio)araalkylamines. J Med Chem. 2000;43:3103–10.CrossRefPubMedGoogle Scholar
- 16.Mai JK, Assheuer J, Paxinos G. Atlas of the human brain. 2nd ed. San Diego: Elsevier Academic; 2004.Google Scholar